Thrombopoietin has a differentiative effect on late-stage human erythropoiesis

Abstract

Summary.To further explore the mechanism of the effect of thrombopoietin (TPO) on erythropoiesis, we used a twophase culture system to investigate the effect of TPO on latestage human erythroid lineage differentiation. In serum-free suspension and semisolid cultures of human peripheral blood derived erythroid progenitors, TPO alone did not produce benzidine-positive cells. However, in serum-containing culture, TPO alone stimulated erythroid cell proliferation and differentiation, demonstrated by erythroid colony formation, production of benzidine-positive cells and haemoglobin (Hb) synthesis. Monoclonal anti-human erythropoietin antibody and anti-human erythropoietin receptor antibody completely abrogated the erythroid differentiative ability of TPO in the serum-containing systems. This implied that binding of EPO and EPO-R was essential for erythropoiesis and the resultant signal transduction may be augmented by the signals emanating from TPO-c-Mpl interaction. Experiment of withdrawal of TPO further demonstrated the involvement of TPO in late-stage erythropoiesis. RT-PCR results showed that there was EPO-R but not c-Mpl expression on developing erythroblasts induced by TPO in serum-containing system. Our results establish that TPO affects not only the proliferation of erythroid progenitors but also the differentiation of erythroid progenitors to mature erythroid cells.

Cooperative Effect of Erythropoietin and TGF‐β Inhibition on Erythroid Development in Human Pluripotent Stem Cells

“…In the presence of TPO, a primary factor of megakaryocytic development [Bacon et al, 1995;Sabath et al, 1995], approximately half of hematopoietic cells in suspension were CD41 þ CD235a þ cells. It has been demonstrated that TPO also promotes the early stage hematopoiesis and erythroid progenitor development [Papayannopoulou et al, 1996;Ratajczak et al, 1997;Tanimukai et al, 1997;Liu et al, 1999]. Interestingly, in the presence of both TPO and EPO, CD41 þ CD235a þ MEP were decreased and CD235a þ CD41erythroid cells were increased significantly, indicating that EPO signaling is more effect to direct hematopoietic lineage development than TPO signaling.…”

X-ray signatures of the polar dusty gas in AGN

“…The Si Kα lines of the Circinus galaxy and NGC 1068 have been studied with Chandra HETG observations in the literature (e.g Sambruna et al 2001;Ogle et al 2003;Kallman et al 2014;Liu 2016), but no detailed redshifts were compared with the host galaxies. For convenience, we replot the Chandra HETG spectra of the Si Kα line of the Circinus galaxy and NGC 1068, corrected for the systemic redshifts of the host galaxies (0.00145 and 0.00379, respectively), in Figure 7.…”

“…The data are reprocessed following the standard process with tgcat script 1 (Huenemoerder et al 2011), except that the zero-order centroids are determined from photons within 3 − 8 keV, to avoid the possible contamination by off-center soft X-ray emission. (We noted that the Si Kα lines presented in Liu (2016) were corrected for the redshifts of the Si Kα lines, not the systemic redshifts of the host galaxies.) As can be seen in Figure 7, the Si Kα peaks are blueshifted with respect to the systemic velocities of the host galaxies, although the photon statistics are limited (the photon counts around the Si Kα peaks are about 80 and 50, for the Circinus galaxy and NGC 1068, respectively).…”

Identification and characterization of novel full-length cDNAs expressed during hematopoietic lineage-specific differentiation of cultured human peripheral blood mononuclear cells

“…Human peripheral blood mononuclear cells were isolated and differentiated through the two-phase culture system [2]. Following 7 days of culture (phase I), human recombinant EPO (1 U/ml), G-CSF (10 ng/ml), and TPO (10 ng/ml) were added to the medium at the beginning of phase II for erythroid-, myeloid-, and megakaryocytic-lineage differentiation, respectively.…”